Role of the androgen receptor in triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is an aggressive disease with outcomes inferior to those of other breast cancer subtypes. No targeted therapies are currently approved for TNBC, and newer treatment approaches are critically needed. It is increasingly recognized that TNBC is a heterogeneous disease, and the role of androgen signaling in a subset of TNBC is emerging. Although the degree of androgen receptor (AR) expression in TNBC varies widely depending on the assay methodology, cutoff for positivity, and patient population, existing evidence suggests an association between a higher level of AR expression and improved outcomes. Despite lower pathologic complete response (pCR) rates with neoadjuvant therapy, patients with AR-dependent TNBCs have a better prognosis than those with TNBCs that are not AR-dependent. Furthermore, gene expression profiling has been used to identify a luminal androgen receptor subtype of TNBC that is dependent on AR signaling. Early clinical studies investigating agents targeting AR in advanced TNBC have produced promising results. We review herein the literature on the biology of AR in breast cancer and its prognostic and predictive role in TNBC, and we describe the results of early clinical trials with antiandrogens in this population. We also present our vision of the future development of newer therapeutic strategies in AR-dependent TNBC.

Figure

Timeline of the development of androgen receptor–targeted therapies in triple-negative breast cancer. PI3K/mTORi, phosphoinositide 3-kinase/mammalian target of rapamycin inhibitor; CDK4/6i, cyclin-dependent kinase 4/6 inhibitor.